The purpose of this study is to determine the effects of morphine administration on the biochemistry of the adrenergic system using the adrenal medulla as a model tissue. Acute morphine administration resulted in depletion of adrenal catecholamines (CA), while chronic treatment resulted in elevated CA, increases in the CA biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), and formation of large numbers of immature catecholamine storage vesicles. Prolonged administration of large doses of morphine resulted in vesicles with a defective CA uptake system (increased Km for epinephrine). These data indicate that in rats, (1) tolerance does not develop to the sympatho-adrenal reflex elicited by morphine, (2) the elevation in CA by chronic morphine results from increased CA synthesis and storage, not decreased CA release, and (3) chronic morphine induces a change in the functional properties of CA storage vesicles. In contrast to adults, perinatally-addicted rats demonstrated low CA and DBH levels at birth and no drug-induced increase in TH, nor were the defective vesicles seen in adults evidenced in neonates. Rats exposed to morphine during development showed a retardation of sympatho-adrenal development which disappeared by weaning. These results indicate that the effects of morphine differ in developing vs. mature rats and that early exposure to morphine alters subsequent symphatho-adrenal development.